Pharmacogenetic study to predicting clinical response of oxaliplatin in patients with advanced colorectal cancer

• Project/Area Number: 21790661
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Kyoto University
• Principal Investigator: KANAI Masashi Kyoto University, 医学研究科, 特定助教 (70432416)
• Co-Investigator(Renkei-kenkyūsha): MATSUDA Fumihiko 京都大学, 医学研究科, 教授 (50212220)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: がん化学療法 / 薬理遺伝学 / オキサリプラチン / 神経障害 / pharmacogenomics / 個別化治療 / pharmacogenetics

Research Abstract

Susceptibility to oxaliplatin-induced neuropathy differs greatly among patients. In this study, we investigated the associations between oxaliplatin-induced neuropathy and the following polymorphisms : glutathione S-transferase p (GSTP1) Ile^<105>Val, and glyoxylate aminotransferase (AGXT) Pro^<11>Leu and AGXT Ile^<340>Met. Eighty-two Japanese patients with histologically confirmed colorectal cancer who received at least six cycles of the modified FOLFOX6 (m-FOLFOX6) regimen were enrolled.
There were more patients carrying at least one GSTP1^<105>Val allele among the group with grade 2/3 neuropathy han among the group with grade 1 neuropathy although the difference was not statistically significant (41% vs 24%, P=0.098). There were similar numbers of patients carrying at least one AGXT^<105>Met allele in the grade 2/3 neuropathy and grade 1 neuropathy groups (16% vs 13% ; P=0.725). The AGXT^<11>Leu allele was not found in any of our patients or controls.

Research Products

• [Journal Article] Dose-escalation and pharmacokinetic study of nanoparticlecurcumin, apotential anticancer agent with improved bioavailability, in health human volunteers. (2011)
  • Author(s): Kanai M, Imaizumi A, Otsuka Y, Sasaki H, Hashiguchi M, Tsujiko K, Matsumoto S,Ishiguro H, Chiba T.
  • Journal Title: Cancer Chemother Pharmacol. (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] A Case of Progressive Digital Ischemia after Early Withdrawal of Gemcitabine and S-1 in a Patient with Systemic Sclerosis. (2011)
  • Author(s): Zaima C, Kanai M, Ishikawa S, Kawaguchi Y, Masui T, Mori Y, Nishimura T,Matsumoto S, Yanagihara K, Chiba T, Mimori T.
  • Journal Title: Jpn J Clin Oncol. 41(6) Pages: 803-806
  • NAID: 120004225524
  • Peer Reviewed
• [Journal Article] Aphase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer. (2010)
  • Author(s): Kanai M, Yoshimura K, Asada M, Imaizumi A, Suzuki C, Matsumoto S, Nishimura T, Mori Y, Masui T, Kawaguchi Y, Yanagihara K, Yazumi S, Chiba T, Guha S, Aggarwal BB
  • Journal Title: Cancer Chemother Pharmacol. 66(5) Pages: 913-918
  • Peer Reviewed
• [Journal Article] KLF4α Up-regulation Promotes Cell Cycle Progression and Reduces Survival Time of Patients With Pancreatic Cancer. (2010)
  • Author(s): Wei D, Wang L, Kanai M, Jia Z, Le X, Li Q, Wang H, Xie K
  • Journal Title: Gastroenterology. 139(6) Pages: 2135-2145
  • Peer Reviewed
• [Journal Article] A multi-institution phase II study of gemcitabine/S-1 combination chemotherapy for patients with advanced biliary tract cancer (2010)
  • Author(s): Kanai M, Yoshimura K, Tsumura T, Asada M, Suzuki C, Niimi M, Matsumoto S, Nishimura T, Nitta T, Yasuchika K, Taura K, Mori Y, Hamada A, Inoue N, Tada S, Yanagihara K, Yazumi S, Osaki Y, Chiba T, Ikai I, Fukushima M, Uemoto S, Hatano E
  • Journal Title: Cancer Chemother Pharmacol 67(6) Pages: 1429-1434
  • NAID: 120003238952
  • Peer Reviewed
• [Journal Article] Premedication with 20 mg dexamethasone effectively prevents relapse of extensive skin rash associated with gemcitabine monotherapy (2010)
  • Author(s): Kanai M, Matsumoto S, Nishimura T, Matsumura Y, Hatano E, Mori A, Masui T, Kawaguchi Y, Nakamura E, Tada S, Kitano T, Ishiguro H, Yanagihara K, Chiba T
  • Journal Title: Ann Oncol. 21(1) Pages: 189-190
  • Peer Reviewed
• [Journal Article] Associations between glutathione S-transferase pi Ile105Val and glyoxylate aminotransferase Pro11Leu and Ile340Met polymorphisms and early-onset oxaliplatin-induced neuropathy (2010)
  • Author(s): Kanai M, Yoshioka A, Tanaka S et al.Kanai M, Yoshioka A, Tanaka S, Nagayama S, Matsumoto S, Nishimura T, Niimi M,Teramukai S, Takahashi R, Mori Y, Kitano T, Ishiguro H, Yanagihara K, Chiba T, Fukushima M, Matsuda F
  • Journal Title: Cancer Epidemiology 34(2) Pages: 189-193
  • NAID: 120002098847
  • Peer Reviewed
• [Journal Article] Phase II study of S-1 and docetaxel for previously treated patients with locally advanced or metastatic non-small cell lung cancer. (2010)
  • Author(s): Yanagihara K, Yoshimura K, Niimi M, Yasuda H, Sasaki T, Nishimura T, Ishiguro H, Matsumoto S, Kitano T, Kanai M, Misawa A, Tada H, Teramukai S, Mio T, Fukushima M.
  • Journal Title: Cancer Chemother Pharmacol. 66(5) Pages: 913-918
  • NAID: 120002515188
  • Peer Reviewed
• [Journal Article] Oxaliplatin-free interval as a risk factor for hypersensitivity reaction among colorectal cancer patients treated with FOLFOX (2010)
  • Author(s): Mori Y, Nishimura T, Kitano T, Yoshimura K, Matsumoto S, Kanai M, Hazama M, Ishiguro H, Nagayama S, Yanagihara K, Teramukai S, Chiba T, Sakai Y, Fukushima M
  • Journal Title: Oncology. 79(1-2) Pages: 136-143
  • Peer Reviewed
• [Journal Article] Associations between glutathione S-transferase pi Ile^<105> Val and glyoxylate aminotransferase Pro^<11> Leu and Ile^<340> Met polymorphisms and early-onset oxaliplatin-induced neuropathy (2010)
  • Author(s): Kanai M, Yoshioka A, Tanaka S, et al.
  • Journal Title: Cancer Epidemiology Volume: 34 Pages: 189-193
  • Peer Reviewed
• [Journal Article] KLF4α Up-regulation Promotes Cell Cycle Progression and Reduces Survival Time of Patients With Pancreatic Cancer. (2010)
  • Author(s): Wei D, Wang L, Kanai M (Equal contribution with W.D, W.L), et al.
  • Journal Title: Gastroenterology Volume: 139 Pages: 2135-45
  • Peer Reviewed
• [Journal Article] A multi-institution phase II study of gemcitabine/S-1 combination chemotherapy for patients with advanced biliary tract cancer (2010)
  • Author(s): Kanai M, Yoshimura K, Tsumura T, et al
  • Journal Title: Cancer Chemotherapy and Pharmacology
  • NAID: 120003238952
  • Peer Reviewed
• [Journal Article] A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer (2010)
  • Author(s): Kanai M, Yoshimura K, Asada M, et al
  • Journal Title: Cancer Chemotherapy and Pharmacology
  • NAID: 120003238951
  • Peer Reviewed
• [Journal Article] Premedication with 20 mg dexamethasone effectively prevents relapse of extensive skin rash associated with gemcitabine monotherapy (2010)
  • Author(s): Kanai M, Matsumoto S, Nishimura T, et al.
  • Journal Title: Ann Oncol Volume: 21 Pages: 189-90
  • Peer Reviewed
• [Journal Article] Associations between glutathione S-transferase pi Ile^<105>Val and glyoxylate aminotransferase Pro^<11>Leu and Ile^<340>Met polymor phisms and early-onset oxaliplatin-induced neuropathy (2010)
  • Author(s): Kanai M, Yoshioka A, Tanaka S, et al
  • Journal Title: Cancer Epidemiology 34(in press) Pages: 189-193
  • Peer Reviewed
• [Journal Article] UGT1A1^*6 polymorphism is most predictive of severe neutropenia induced by irinotecan in Japanese cancer patients (2009)
  • Author(s): Onoue M, Terada T, Kanai M, et al.(12名中8番)
  • Journal Title: Int J Clin Oncol 14 Pages: 136-142
  • NAID: 10025147852
  • Peer Reviewed
• [Presentation] クルクミンを用いた新しいがん治療法の開発 (2011)
  • Author(s): 金井雅史、八隅秀二郎、千葉勉
  • Organizer: 日本消化器病学会シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2011-10-16
• [Presentation] 細粒化クルクミンを用いた新しいがん治療法の開発 (2011)
  • Author(s): 金井雅史
  • Organizer: 日本抗加齢医学会シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2011-05-27
• [Presentation] ゲムシタビンによる皮疹とその対策 (2011)
  • Author(s): 金井雅史
  • Organizer: 第2回京都胆道カンファランス
  • Place of Presentation: 京都
  • Year and Date: 2011-01-13
• [Presentation] クルクミンを用いた新規癌治療法の開発 (2010)
  • Author(s): 金井雅史、八隅秀二郎、千葉勉
  • Organizer: 日本消化器病学会
  • Place of Presentation: 東京
  • Year and Date: 2010-10-15
• [Presentation] A Phase I/II Study of Complementary Therapy Using Curcumin for Pancreatic Cancer Patients Who Get Refractory to Gemcitabine-Based Chemotherapy (2010)
  • Author(s): Kanai M
  • Organizer: International Society for Nutraceuticals and Functional Food Annual Conference 2010招待講演
  • Place of Presentation: Indonesia
  • Year and Date: 2010-10-13
• [Presentation] A Phase I/II Study of Complementary Therapy Using Curcumin for Pancreatic Cancer Patients Who Get Resistant to Gemcitabine-Based Chemotherapy (2010)
  • Author(s): Kanai M
  • Organizer: International Society for Nutraceuticals and Functional Foods Annual Conference 2010
  • Place of Presentation: Bali, Indonesia(招待講演)
  • Year and Date: 2010-10-13
• [Presentation] A Phase I/II Study of Complementary Therapy Using Curcumin for Pancreatic Cancer Patients Who Get Refractory to Gemcitabine-Based Chemotherapy (2010)
  • Author(s): Kanai M
  • Organizer: The 3rd World Cancer Congress 2010招待講演
  • Place of Presentation: Singapore
  • Year and Date: 2010-06-23
• [Presentation] A Phase I/II Study of Complementary Therapy Using Curcumin for Pancreatic Cancer Patients Who Get Refractory to Gemcitabine-Based Chemotherapy (2010)
  • Author(s): Kanai M
  • Organizer: The 3^<rd> World Cancer Congress 2010
  • Place of Presentation: Singapore(招待講演)
  • Year and Date: 2010-06-23
• [Presentation] 切除不能進行胆道癌に対するゲムシタビン/S-1併用療法の治療成績 (2010)
  • Author(s): 金井雅史
  • Organizer: 第1回京都胆道カンファランス
  • Place of Presentation: 京都
  • Year and Date: 2010-06-10
• [Presentation] 切除不能胆道癌に対するgemcitabine+S-1併用療法の第II相臨床試験(最終結果) (2010)
  • Author(s): 金井雅史、波多野悦朗、津村剛彦、浅田全範、松本繁巳、西村貴文、濱田暁彦、井上直也、森由希子、吉村健一、柳原一広、多田真輔、八隅秀二郎、大崎往夫、千葉勉
  • Organizer: 日本臨床腫瘍学会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-18
• [Presentation] Pharmacogenetic approach to predicting clinical response of chemotherapy in advanced colorectal cancer (2010)
  • Author(s): Kanai M
  • Organizer: Organisation for Oncology and Translational Research conference招待講演
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-02-27
• [Presentation] Pharmacogenetic approach to predicting clinical response of chemotherapy in advanced colorectal cancer (2010)
  • Author(s): Kanai M
  • Organizer: Organisation for Oncology and Translational Research conference
  • Place of Presentation: Kyoto, Japan(招待講演)
  • Year and Date: 2010-02-27
• [Presentation] Pharmacogenetic approach to predicting clinical response of chemotherapy in advanced colorectal cancer (2010)
  • Author(s): Masashi Kanai
  • Organizer: Organisation for Oncology and Translational Research conference
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-02-27
• [Book] 分子消化器病(遺伝子多型解析は消化器癌化学療法にどのように役に立つのか?) (2011)
  • Author(s): 金井雅史、松本繁巳、千葉勉
  • Publisher: (in press)
• [Book] 伏見医報(分子標的薬剤を用いた消化器がん化学療法の現状)607 (2010)
  • Author(s): 金井雅史
  • Total Pages: 277
• [Book] 分子消化器病(消化器癌治療薬選択のための遺伝子検査)7巻4号 (2010)
  • Author(s): 金井雅史、千葉勉
• [Book] 外科治療(胆道癌補助化学療法の実際)第102号 (2010)
  • Author(s): 田浦康二郎、波多野悦朗、金井雅史、上本伸二
• [Book] 分子消化器病「消化器癌治療薬選択のための遺伝子検査」 (2010)
  • Author(s): 金井雅史、千葉勉
  • Total Pages: 5
  • Publisher: 先端医学社